Search

Crb2 is a cell polarity-related type I transmembrane protein expressed in the apical membrane of podocytes. Knockdown of crb2 causes glomerular permeability defects in zebrafish, and its complete knockout causes embryonic lethality in mice. There are also reports of Crb2 mutations in patients with steroid-resistant nephrotic syndrome, although the precise mechanism is unclear. The present study demonstrated that podocyte-specific Crb2 knockout mice develop massive albuminuria and microhematuria 2-month after birth and focal segmental glomerulosclerosis and tubulointerstitial fibrosis with hemosiderin-laden macrophages at 6-month of age. Transmission and scanning electron microscopic studies demonstrated injury and foot process effacement of podocytes in 6-month aged podocyte-specific Crb2 knockout mice. The number of glomerular Wt1-positive cells and the expressions of Nphs2, Podxl, and Nphs1 were reduced in podocyte-specific Crb2 knockout mice compared to negative control mice. Human podocytes lacking CRB2 had significantly decreased F-actin positive area and were more susceptible to apoptosis than their wild-type counterparts. Overall, this study's results suggest that the specific deprivation of Crb2 in podocytes induces altered actin cytoskeleton reorganization associated with dysfunction and accelerated apoptosis of podocytes that ultimately cause focal segmental glomerulosclerosis.

Objective To compare the 2012 American Urological Association (AUA) and 2020 AUA/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) microscopic hematuria (MH) guidelines as applied in 1,018 patients with MH, to confirm of risk groups and to investigate the natural history of patients with MH. Materials and Methods Patients who had undergone a complete urological evaluation for MH according to the 2012 AUA MH guidelines were identified retrospectively. All the patients were then classified into low-, intermediate-, or high-risk for urinary tract malignancy according to the updated 2020 AUA/SUFU MH guidelines, for a second evaluation. The results of the first and second evaluations using the previous 2012 AUA and updated 2020 AUA/SUFU MH guidelines, respectively, were then compared. Results A total of 1018 patients with MH were identified. The urinary tract malignancy rate was 3.3% (34 of the 1,018 patients). According to the 2020 AUA/SUFU MH guidelines, there were 218 patients (21.4%) in the low-risk group, 447 patients (43.9%) in the intermediate-risk group, and 353 patients (34.6%) in the high-risk group. All the 34 patients with malignancy were from the intermediate- or high-risk group who require further urological evaluation. There was no patient with newly developed urinary tract malignancy at the median follow-up time of 28 months (12-58). Conclusion The use of the updated 2020 AUA/SUFU MH guidelines may reduce the number of diagnostic procedures without compromising the diagnosis of life-threatening malignant lesions.

Cellular crescents are defined as two or more layers of proliferating cells in Bowman's space and are a hallmark of inflammatory active glomerulonephritis and a histologic marker of severe glomerular injury. In general, the percentage of glomeruli that exhibit crescents correlates with the severity of kidney failure and other clinical manifestations of nephritic syndrome. In general, a predominance of active crescents is associated with rapidly progressive glomerulonephritis and a poor outcome. The duration and potential reversibility of the underlying disease correspond with the relative predominance of cellular or fibrous components in the crescents, the initial location of the immunologic insult inside the glomerulus, and the sort of involved cells and inflammatory mediators. However, the presence of active crescents may not have the same degree of significance in the different types of glomerulopathies. The pathophysiology of parietal cell proliferation may have dissimilar origins, underscoring the fact that the resultant crescents are a non-specific morphological pattern of glomerular injury with different implications in clinical prognosis in the scope of glomerular diseases.

Background Thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown. Case presentation A 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation. Conclusions We suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH.

Thin basement membrane nephropathy (TBMN) is characterized by the observation of microhematuria and a thin glomerular basement membrane on kidney biopsy specimens. Its main cause is heterozygous mutations of COL4A3 or COL4A4, which also cause late-onset focal segmental glomerulosclerosis (FSGS) or autosomal dominant Alport syndrome (ADAS). Thirteen TBMN cases were analyzed using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and exome sequencing. Ten heterozygous variants were detected in COL4A3 or COL4A4 in nine patients via Sanger sequencing, three of which were novel variants. The diagnostic rate of “likely pathogenic” or “pathogenic” under the American College of Medical Genetics and Genomics guidelines was 53.8% (7 out of 13 patients). There were eight single nucleotide variants, seven of which were glycine substitutions in the collagenous domain, one of which was a splice-site single nucleotide variant, and two of which were deletion variants. One patient had digenic variants in COL4A3 and COL4A4. While MLPA analyses showed negative results, exome sequencing identified three heterozygous variants in causative genes of FSGS in four patients with no apparent variants on Sanger sequencing. Since patients with heterozygous mutations of COL4A3 or COL4A4 showed a wide spectrum of disease from TBMN to ADAS, careful follow-up will be necessary for these patients.

Microhematuria is a prevalent condition and the American Urological Association has developed a new risk-stratified approach for the evaluation of patients with microhematuria. Our objective was to provide the first evaluation of this important guideline.This multinational cohort study combines contemporary patients from 5 clinical trials and 2 prospective registries who underwent urological evaluation for hematuria. Patients were stratified into American Urological Association risk strata (low, intermediate or high risk) based on sex, age, degree of hematuria, and smoking history. The primary end point was the incidence of bladder cancer within each risk stratum.A total of 15,779 patients were included in the analysis. Overall, 727 patients (4.6%) were classified as low risk, 1,863 patients (11.8%) were classified as intermediate risk, and 13,189 patients (83.6%) were classified as high risk. The predominance of high risk patients was consistent across all cohorts. A total of 857 bladder cancers were diagnosed with a bladder cancer incidence of 5.4%. Bladder cancer was more prevalent in men, smokers, older patients and patients with gross hematuria. The cancer incidence for low, intermediate and high risk groups was 0.4% (3 patients), 1.0% (18 patients) and 6.3% (836 patients), respectively.The new risk stratification system separates hematuria patients into clinically meaningful categories with differing likelihoods of bladder cancer that would justify evaluating the low, intermediate and high risk groups with incremental intensity. Furthermore, it provides the relative incidence of bladder cancer in each risk group which should facilitate patient counseling regarding the risks and benefits of evaluation for bladder cancer.

Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder with genetic defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex in phagocytes, leading to recurrent severe infections and granuloma formation. Genitourinary involvement, including obstructive granulomas, infections, nephrotoxicity of anti-infective agents, and amyloidosis, is frequently observed in patients with CGD, whereas the clinical and pathological details of the less commonly reported glomerular disease remain obscure. Here, we report the case of a patient with CGD who developed rapidly progressive IgA vasculitis-associated nephritis (IgAVN) and review the literature on biopsy-proven glomerular diseases in patients with CGD. A 22-year-old male patient with CGD developed rapidly progressive glomerulonephritis (RPGN) following peripheral purpura and was diagnosed with crescentic IgAVN based on the renal biopsy evaluation. There was no evidence of active infections, and he received pulse intravenous methylprednisolone followed by oral prednisolone. His renal function returned to normal within 4 weeks, and his proteinuria and microhematuria finally resolved. The present case and literature review indicate that IgAVN and IgA nephropathy with RPGN are the most common causes of glomerular disease in patients with CGD. Clinicians should be aware of the possibility of these diseases as causes of RPGN in CGD, because delays in diagnosis and appropriate treatment may affect renal outcomes.

The review article presents data on: a) definition of microhematuria and diagnosis; b) prevalence estimation and causes of the asymptomatic microscopic hematuria; c) diagnostic approaches for the first time identified of microhematuria; d) follow-up monitoring of patients with asymptomatic hematuria; e) feasibility of medical screening for microhematuria. The analysis includes recommendations of Russian and foreign urological associations, the results of cohort and observational studies, previous study reviews. The identification of 3 or more red blood cells during microscopic examination should be considered microhematuria. There is no uniform examination algorithm for all patients. The basic principle is an individual diagnostic tactic, taking into account the anamnesis, age, concomitant diseases and risk factors. The purpose of a comprehensive examination is to exclude life-threatening conditions (malignant neoplasms and/or glomerular kidney damage). In some cases, after research, the cause of microhematuria remains unclear and monitoring is required. Routine screening of the population in order to detect microhematuria is currently not justified.В обзорной статье представлены данные по вопросам: а) определения понятия микрогематурия и методов ее выявления; б) оценки распространенности и причин бессимптомной микрогематурии; в) диагностических подходов при первичном (случайном) выявлении микрогематурии; г) последующего мониторинга пациентов с бессимптомной гематурией; д) целесообразности скрининга на микрогематурию. В анализ включены российские и зарубежные рекомендации профессиональных сообществ, результаты когортных и обсервационных исследований, ранее выполненные обзоры. Микрогематурией следует считать выявление 3 и более эритроцитов при микроскопическом исследовании. В мире отсутствует единый для всех пациентов алгоритм обследования. Основной принцип индивидуальная диагностическая тактика с учетом анамнеза, возраста, сопутствующих заболеваний и факторов риска. Целью комплексного обследования является исключение жизнеугрожающих состояний (злокачественного новообразования и/или гломерулярного поражения почек). В части случаев после проведения исследований причина микрогематурии остается неясной и требуется мониторинг. Рутинный скрининг населения с целью выявления микрогематурии в настоящее время не считается обоснованным.

Patients presenting with microhematuria represent a heterogeneous population with a broad spectrum of risk for genitourinary malignancy. Recognizing that patient-specific characteristics modify the risk of underlying malignant etiologies, this guideline sought to provide a personalized diagnostic testing strategy.The systematic review incorporated evidence published from January 2010 through February 2019, with an updated literature search to include studies published up to December 2019. Evidence-based statements were developed by the expert Panel, with statement type linked to evidence strength, level of certainty, and the Panel's judgment regarding the balance between benefits and risks/burdens.Microhematuria should be defined as ≥ 3 red blood cells per high power field on microscopic evaluation of a single specimen. In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. The Panel created a risk classification system for patients with microhematuria, stratified as low-, intermediate-, or high-risk for genitourinary malignancy. Risk groups were based on factors including age, sex, smoking and other urothelial cancer risk factors, degree and persistence of microhematuria, as well as prior gross hematuria. Diagnostic evaluation with cystoscopy and upper tract imaging was recommended according to patient risk and involving shared decision-making. Statements also inform follow-up after a negative microhematuria evaluation.Patients with microhematuria should be classified based on their risk of genitourinary malignancy and evaluated with a risk-based strategy. Future high-quality studies are required to improve the care of these patients.

Background Patients with gout frequently have low urinary pH, which is associated with the nephrolithiasis. However, the specific distribution of urinary pH and potential relationship of acidic urine pH to broader manifestations of kidney disease in gout are still poorly understood. Methods A 2016–2020 population-based cross-sectional study was conducted among 3565 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University to investigate the association between low urinary pH and kidney disease. We studied patients that we defined to have “primary gout”, based on the absence of > stage 2 CKD. All subjects underwent 14 days of medication washout and 3-day standardized metabolic diet. We obtained general medical information, blood and urine biochemistries, and renal ultrasound examination on the day of the visit. The primary readouts were urine pH, eGFR, nephrolithiasis, renal cysts, microhematuria, and proteinuria. Patients were assigned into 5 subgroups (urine pH ≤5.0, 5.0 6.9), aligning with the clinical significance of urine pH. Results Overall, the median urine pH and eGFR of all patients was 5.63 (IQR 5.37~6.09), and 98.32 (IQR 86.03~110.6), with acidic urine in 46.5% of patients. The prevalence of nephrolithiasis, microhematuria, and proteinuria were 16.9%, 49.5%, and 6.9%, respectively. By univariate analysis, eGFR was significantly associated with age, sex, duration of gout, tophus, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, serum utare, hypertension, diabetes, and urine pH. On multivariable analysis, eGFR was associated with age, sex, diastolic blood pressure, serum uric acid, hypertension, diabetes, and urine pH. Acidic urine pH, especially urine pH < 5.0, was significantly associated with the prevalence of kidney disease, including > stage 1 CKD, nephrolithiasis, kidney cyst, and microhematuria. Patients with 6.2 ≤ urine pH ≤ 6.9 and SU ≤ 480 μmol/L had the highest eGFR with the lowest prevalence of nephrolithiasis, microhematuria, and proteinuria. Conclusions Approximately half of gout subjects had acidic urine pH. Urine pH < 5.0 was associated with significantly increased nephrolithiasis, renal cyst, microhematuria, and proteinuria. The results support prospective clinical investigation of urinary alkalinization in selected gout patients with acidic urine pH.

PURPOSE We sought to model the diagnostic recommendations and associated costs of new hematuria guidelines regarding referral patterns, procedure utilization and urothelial cell carcinoma (UCC) detection. MATERIALS AND METHODS Patients with microhematuria were identified retrospectively. Initial encounter data were collected from January 2017 to May 2018 from a large public health care system; followup was continued to December 2020. Risk stratification was performed based on the American Urological Association 2020 microhematuria guidelines, and disease outcomes were analyzed within this framework. The guideline-recommended workups and costs were modeled; cost data were sourced from the Centers for Medicare & Medicaid Services Medicare Physician Fee Schedule and Clinical Laboratory Fee Schedule for 2020. Modeled diagnostic volumes and costs were assessed for 2020 and 2012 microhematuria guidelines, respectively. RESULTS Of the 3,789 patients included for analysis, 1,382 (36.5%), 1,026 (27.1%) and 1,381 (36.4%) were retroactively stratified as low risk, intermediate risk (InR) and high risk (HiR), respectively. A total of 19 cases of UCC (17 bladder, 2 upper tract) were diagnosed, of which 84% were HiR. For high-grade UCC, 92% of cases were HiR. The 2020 guidelines recommended renal ultrasound for 1,117 InR cases, computerized tomography urogram (CTU) for 1,476 HiR cases, and cystoscopy for 2,593 InR and HiR cases combined. Total costs were $1,905,236 (2012) versus $1,260,677 (2020), driven mainly by CTU costs. Per-cancer detected costs were $100,276 (2012) versus $61,760 (2020). CONCLUSIONS In retrospect, the 2020 guidelines would have effectively risk-stratified microhematuria cases for detection of malignancies. As compared to the 2012 guidelines, application of the 2020 guidelines would result in significant changes to diagnostic and procedural volumes, while substantially reducing total and per-patient costs.

This study determined the contribution of a mobile health (M-health) system to the treatment of Schistosoma haematobium in a region of Chad where S. haematobium is endemic. M-health involves the use of a mobile phone for health care. The study compared the prevalence of schistosomiasis in an area with an M-health system, newly installed in 2014, with an area without an adequate health infrastructure. Data were gathered after the M-health system had been running for 3 years. We took urine samples from children age 1 to 15 years, for a total of 200 children in a village in the M-health area and 200 in a village in a non-M-health area. Urine was checked for urinary schistosomiasis by using dipsticks for microhematuria and, in cases of positive dipstick results, microscopy was used to detect eggs. Comparison between the areas allowed us to assess the effectiveness of the installed M-health system after 3 years of operation. Based on dipstick outcomes, the non-M-health area had an infection rate of 51.5% compared with 29% in the M-health area. Microscopy results in non-M-health and M-health were 27.5% and 21%, respectively. The dipstick result difference between M-health and non-M-health areas was statistically significant. Dipsticks were more reliable than microscopy for the detection of schistosomiasis, especially in areas without qualified personnel. Based on these results, M-health proved its ability to reduce the infection rate of urogenital schistosomiasis, and the implementation of M-health shows great promise in areas where this disease is endemic and where no mass drug administration is provided.

Background Recent research suggests that schistosomiasis targets for morbidity control and elimination as a public health problem could benefit from a reanalysis. These analyses would define evidence-based targets that control programs could use to confidently assert that they had controlled or eliminated schistosomiasis as a public health problem. We estimated how low Schistosoma haematobium infection levels diagnosed by urine filtration in school-age children should be decreased so that microhematuria prevalence was at, or below, a “background” level of morbidity. Methodology Data obtained from school-age children in Burkina Faso, Mali, Niger, Tanzania, and Zambia who participated in schistosomiasis monitoring and evaluation cohorts were reanalyzed before and after initiation of preventive chemotherapy. Bayesian models estimated the infection level prevalence probabilities associated with microhematuria thresholds ≤10%, 13%, or 15%. Principal findings An infection prevalence of 5% could be a sensible target for urogenital schistosomiasis morbidity control in children as microhematuria prevalence was highly likely to be below 10% in all surveys. Targets of 8% and 11% infection prevalence were highly likely to result in microhematuria levels less than 13% and 15%, respectively. By contrast, measuring heavy-intensity infections only achieves these thresholds at impractically low prevalence levels. Conclusions/significance A target of 5%, 8%, or 11% urogenital schistosomiasis infection prevalence in school-age children could be used to determine whether a geographic area has controlled or eliminated schistosomiasis as a public health problem depending on the local background threshold of microhematuria., Author summary For urogenital schistosomiasis, targets for morbidity control and elimination as a public health problem are based on the percentage of school-age children with a heavy intensity infection in a set of sentinel schools. These targets are not tied to specific morbidity indicators and should be reevaluated due to the recognition that all infections have an impact on people’s health. Multiple studies have shown a strong association between urogenital schistosomiasis infection and microhematuria. In these analyses, data from children aged 6–15 years in monitoring and evaluation cohorts from five African countries were used to determine whether infection and heavy intensity infection targets could be developed, based on a prevalence of microhematuria in a school without schistosomiasis infections before and after initiation of a deworming program. Results indicate that targets of 5%, 8%, or 11% urogenital schistosomiasis infection prevalence in school-age children can be used to reliably conclude that a school is below a microhematuria prevalence of 10%, 13%, or 15%, respectively. These targets could be used by control program managers as guide to determine whether morbidity has been controlled or eliminated as a public health problem.

Objectives To 1) determine the prevalence of urologic malignancy in women evaluated for microhematuria (MH) in a large university-based urology practice, 2) describe clinical features shared by women with MH, and 3) evaluate a risk score for urologic malignancy in women with MH. Methods A retrospective chart review identified women with MH evaluated by a large, university-based urology practice between 2010 and 2020. Clinical and demographic variables associated with their evaluation, referral pattern, appropriateness of referral and evaluation, workup completed, and resulting diagnoses were reported. Patterns of repeat evaluations were also described. Patients were stratified as low-, intermediate-, or high-risk according to AUA/SUFU recommended risk stratification. Results 4456 charts resulted from an initial query based on females with ICD-9 and ICD-10 codes for MH between 2010-2020. 1730 patients (95.5% referrals v. 4.5% established urology patients) met criteria for inclusion in the study, and 1350 underwent evaluation for MH at the practice. Over 30% of referrals were considered inappropriate. 13 patients were diagnosed with urologic malignancy, all of whom were classified as intermediate- or high-risk according to AUA/SUFU criteria. Over 10% of patients had at least 2 evaluations for MH, with only 1 malignancy discovered on repeat evaluation for persistent MH. Conclusions Inappropriate referrals for MH are common. Incidence of urologic malignancy is incredibly low among women evaluated for MH, but especially among those classified as low- and intermediate-risk by new guidelines. Repeat evaluations for persistent, stable MH appear low yield in detecting malignancy.

High-throughput techniques such as whole-exome sequencing (WES) show promise for the identification of candidate genes that underlie Mendelian diseases such as nephrotic syndrome (NS). These techniques have enabled the identification of a proportion of the approximately 54 genes associated with NS. However, the main pitfall of using WES in clinical and research practice is the identification of multiple variants, which hampers interpretation during downstream analysis. One useful strategy is to evaluate the co-inheritance of rare variants in affected family members. Here, we performed WES of a patient with steroid-resistant NS (SRNS) and intermittent microhematuria. Currently, 15 years after kidney transplantation, this patient presents normal kidney function. The patient was found to be homozygous for a rare MYO1E stop-gain variant, and was heterozygous for rare variants in NS-associated genes, COL4A4, KANK1, LAMB2, ANLN, E2F3, and APOL1. We evaluated the presence or absence of these variants in both parents and 11 siblings, three of whom exhibited a milder phenotype of the kidney disease. Analysis of variant segregation in the family, indicated the MYO1E stop-gain variant as the putative causal variant underlying the kidney disease in the patient and two of her affected sisters. Two secondary variants in COL4A4-identified in some other affected family members-require further functional studies to determine whether they play a role in the development of microhematuria in affected family members. Our data illustrate the difficulties in distinguishing the causal pathogenic variants from incidental findings after WES-based variant analysis, especially in heterogenous genetic conditions, such as NS.

To identify patterns of care for women referred for asymptomatic microhematuria in a single, hospital-based health care system and estimate the cost of unindicated evaluation.We conducted a retrospective study of 100 women with a diagnosis of asymptomatic microhematuria referred to a tertiary female pelvic medicine and reconstructive surgery practice. Our analysis focused on referral patterns by obstetrician-gynecologists and primary care physicians. Data analyzed included whether asymptomatic microhematuria was documented using urine microscopy (vs urine dipstick) and whether the urine microscopy correctly identified asymptomatic microhematuria with three red blood cells (RBCs).Forty-six patients were referred who met the American Urological Association's guidelines for asymptomatic microhematuria with a workup estimated at $8,298 per patient. Fifty-four were referred to a female pelvic medicine and reconstructive surgery specialist despite clearly not meeting the American Urological Association's definition of asymptomatic microhematuria. Of these, 33 patients were referred based on dipstick-positive results only, 11 were referred based on microscopic urinalysis demonstrating fewer than three RBCs per high-power field (HPF), and the remaining 10 patients were referred with urine microscopy demonstrating at least 3 RBC/HPF but in the setting of a clearly benign cause, such as infection or menstruation. The total estimated cost of the unnecessary asymptomatic microhematuria workup in patients who did not meet American Urological Association criteria for referral was $1,213 per patient.Fewer than half of the referrals for asymptomatic microhematuria were appropriate, leading to wasted and entirely preventable health care expenditures. This study highlights the need for education of health care providers making these referrals.

A 71-year-old woman with abnormal pulmonary shadows and multiple enlarged thoracic lymph nodes was diagnosed with stage IIB lung adenocarcinoma, pulmonary sarcoidosis, and sarcoidosis-associated lymphadenopathy after biopsies from multiple organ sites. She also had rapidly progressive renal dysfunction, microhematuria, and high myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) concentrations. A renal biopsy revealed granulomatous tubulointerstitial nephritis and necrotizing glomerulonephritis with crescent formation. She was diagnosed with nephritis caused by both sarcoidosis and ANCA-associated vasculitis. Oral prednisolone was administered to treat her nephritis, resulting in improvement in both her renal dysfunction and her sarcoidosis-associated lymphadenopathy.

OBJECTIVES: The study assessed associations between Schistosoma haematobium infection (presence of parasite eggs in urine or hematuria) and self-reported metrics (macrohematuria, fetching surface water, or swimming) to evaluate their performance as proxies of infection in presence of regular preventive chemotherapy. It also examined community water characteristics (safe water access, surface water access, and groundwater quality) to provide context for schistosomiasis transmission in different types of communities and propose interventions. METHODS: Logistic regression was used to assess the associations between the various measured and self-reported metrics in a sample of 897 primary school children in 30 rural Ghanaian communities. Logistic regression was also used to assess associations between community water characteristics, self-reported water-related behaviors and S. haematobium infection. Communities were subsequently categorized as candidates for three types of interventions: additional safe water sources, water treatment, and education about water-related disease risk, depending on their water profile. RESULTS: Microhematuria presence measured with a reagent strip was a good proxy of eggs in urine at individual (Kendall’s τ(b) = 0.88, p

Introduction The aim of this study was to identify factors associated with absent hematuria in patients with symptomatic urinary stones. Methods This retrospective study analyzed the clinical and imaging findings of emergency department patients who underwent computed tomography (CT) for suspected ureteral colic over the past 2 years. All patients also underwent a microscopic urinalysis, and the presence of 4 or more red blood cells/high-power field was defined as microhematuria. Results A total of 798 patients were included in this study. Of these patients, 750 (94.0%) presented with hematuria, while 48 (6.0%) urine samples did not have evidence of hematuria. The group with an absence of hematuria was more likely to have a lower stone location (located in an area from the distal ureter to the bladder) and perinephric stranding on CT than the hematuria group (75.0% vs. 54.3%, p = 0.005; 47.9% vs. 30.5%, p = 0.012, respectively). The degree of hematuria at each stone location was significantly different (p = 0.001). In multivariate analysis, perinephric stranding (odds ratios (OR) 1.87 [95% confidence interval (CI) 1.01–3.46], p = 0.047), a lower stone location (OR 2.72 [95% CI 1.37–5.36], p = 0.004), and elevated serum blood urea nitrogen (BUN) levels (OR 1.06 [95% CI 1.01–1.12], p = 0.026) were associated with absent hematuria. Conclusions In this large cohort of patients with renal colic, 6% had no microhematuria. Although some CT findings and elevated BUN were independently associated with hematuria absence, there was no difference in the demographics, time of presentation and degree and location of pain between the groups.

Background Gemcitabine and cisplatin are chemotherapeutic agents used for treating multiple cancers, and these agents are sometimes used in combination. Drug-induced thrombotic microangiopathy (TMA) is a rare but potentially fatal complication. It typically presents as a systemic disease with the classical triad of hemolytic anemia, thrombocytopenia, and organ damage. In contrast to systemic TMA, cases of renal-limited TMA, defined as biopsy-proven renal TMA without the classical triad, have been reported with relatively good prognosis. Most cases of renal-limited TMA are associated with calcineurin inhibitors, and cases of drug-induced renal-limited TMA due to gemcitabine-dexamethasone-cisplatin therapy have been rarely reported. Case presentation A 43-year-old woman with lymphoma developed acute kidney injury with marked proteinuria, microhematuria, and abnormal urinary casts after receiving one cycle of gemcitabine-dexamethasone-cisplatin therapy. Although she did not show hemolytic anemia and thrombocytopenia, renal biopsy showed diffuse injury to the glomerular endothelial cells, supporting the diagnosis of renal-limited TMA. Her condition improved only with the cessation of gemcitabine and cisplatin treatment. She received another chemotherapy without gemcitabine and platinum agents, and no recurrence of renal-limited TMA was observed. Conclusions Drug-induced TMA occurs early after gemcitabine and cisplatin use in renal-limited form and is reversible when detected and managed in a timely manner. Urinalysis, which is simple and inexpensive and can be easily performed, is a beneficial screening tool for early-onset drug-induced TMA among patients who receive gemcitabine-dexamethasone-cisplatin therapy.

Objective To determine the predictive value of disease characteristics at 12-month follow-up after the diagnosis of GPA for subsequent relapses in a cohort of patients followed at a tertiary vasculitis clinic. Methods Demographic, clinical, and biological data at diagnosis and during follow-up from patients with GPA followed for at least 24 months at the Mount Sinai Hospital Vasculitis Clinic in Toronto, Canada were extracted from the Canadian Vasculitis Research Network (CanVasc) database and analyzed. The association between ANCA status and type (PR3- or MPO-ANCA), presence of microscopic hematuria, or serum creatinine level at follow-up month 12 ± 3 (M12) and relapses after M12 were assessed using Cox proportional hazard models. Results A total of 113 GPA patients were included in this study (50 ANCA positive, 63 ANCA negative at M12). Patient demographics and disease characteristics were similar at diagnosis, including the treatments used for induction and at M12. The global 5-year relapse rate was 55.8%, without any difference in the relapse rates after M12 between those ANCA-positive or negative at M12. However, in multivariate analyses, MPO-ANCA positivity at M12 was predictive of increased relapses after M12 (hazard ratio [HR] 3.54, P=0.01), as was the presence of microhematuria at M12 (HR 1.91, P=0.04). In contrast, higher serum creatinine levels at M12 were associated with a decreased risk of subsequent relapse (HR 0.99, P=0.04). Conclusion In this cohort of patients with GPA, MPO-ANCA positivity and persistent microscopic hematuria at M12 were associated with increased risk of subsequent relapse, and could thus have value to predict disease outcome during follow-up.

Background The aim of the study was to assess the correlation of commonly used laboratory tests with clinical activity, degree of kidney involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies. Methods The study included 28 patients with active AAV (BVAS ≥ 3). The following tests were performed: MPO-ANCA, PR3-ANCA, peripheral blood count, ESR, CRP, procalcitonin, creatinine, GFR, urea, albumin, fibrinogen, d-dimer, components of the C3 and C4 complement systems, urinalysis with sediment evaluation and diurnal proteinuria. The assessments were conducted twice: at study entry (A0) and after 6 months (A6) (BVAS = 0). Results At the time of inclusion in the study, the mean creatinine concentration was 3.39 mg/dl (GFR 33.17 ml/min/1.73 m²), after achieving remission in 11 patients (39.3 %) GFR remained below 30 ml/min/1.73 m², 4 patients (14.3 %) continued renal replacement therapy, and 3 patients (10.7 %) with advanced renal failure died. Microscopic hematuria occurred in 80.9 % of the studied population, withdrew in most patients, strongly correlated with renal involvement p p = 0.147. CRP, ESR, fibrinogen, d-dimer, albumin and hemoglobin in the peripheral blood showed a strong correlation with the clinical activity of AAV and well identified severe patients. High procalcitonin concentrations correlated with a severe form of the disease, pulmonary involvement with respiratory failure and alveolar hemorrhage (mean 3.41 ng/ml, median 0.91 ng/ml, SD 7.62, p = 0.000), and were associated with the occurrence of infectious complications and the need to administer antibiotic therapy. ANCA antibodies were useful in the evaluation of patients with AAV, the amount of antibodies did not correlate with the severity of vasculitis (p = 0.685) and the results in many patients did not match the expected assumptions. Conclusions CRP, ESR, fibrinogen, d-dimers, albumin and hemoglobin in the peripheral blood correlate well with the activity of vasculitis and identify severe patients. The resolution of microscopic hematuria suggests remission of the disease in the renal area. Procalcitonin may be slightly increased in patients with active AAV without infection, high concentrations are strongly associated with infectious complications. ANCA antibodies should always be interpreted in the context of the observed clinical symptoms.

Introduction The 2020 AUA microhematuria (MH) guideline stratifies patients into low, intermediate and high-risk for urologic malignancy based on established risk-factors for urothelial carcinoma. Notably, urine-based tumor markers (UBTMs) were not included in the risk classification. We evaluated the impact of incorporating UBTMs (cytology and multiple commercially available UBTMs) into this risk stratification. Methods We performed a systematic review of performance characteristics of UBTMs for the detection of bladder cancer during hematuria evaluation, pooled the reported sensitivity and specificity, and calculated positive and negative likelihood ratios (LR). These were then applied to the estimated pre-test probability for the diagnosis for each AUA risk strata: low-risk 0.5%, intermediate-risk 1.0%, and high-risk (2%-3%) in order to calculate a post-test probability of bladder cancer in the event of a positive or negative test. Results The pooled sensitivity for urinary cytology and commercially available UBTMs was 68% and 58%-95%, respectively while the specificity was estimated at 91% and 34%-90%, respectively. The positive LRs of UBTMs ranged from 2.1-7.67 and negative LRs ranged from 0.07-0.48. A negative UBTM was associated with a post-test probability of cancer for low, intermediate, and high-risk patients of 0-0.2%, 0.2%-0.5%, and 0.4%-1.1%, respectively. In the setting of a positive UBTM, the post-test probability of cancer for low, intermediate, and high-risk patients was 1.1%-3.7%, 2.1%-7.8%, 4.2%-19.2%, respectively. Conclusion Pending prospective validation, UBTMs may be able to enhance risk stratification and inform shared decision-making over clinical factors alone and allow for re-classification of patients into higher or lower risk categories.

The co-occurrence of IgA nephropathy (IgAN) and positive anti-neutrophil cytoplasmic autoantibodies (ANCA) serology is uncommon. In the present case series and literature review, we aimed to clarify the impact of ANCA on pathogenesis, clinical and histopathology presentation, and outcome in IgAN patients. We report four patients with an overlap lesion of IgAN-ANCA positive. Also, we performed a narrative review of all biopsy-proven published case series. Only 1.2% patients had ANCA in our 330-biopsy-proven IgAN cohort. We compared our data with previous reports-6 case series and 3 small retrospective studies-a total of 103 patients. All patients but one had eGFR below 15 mL/min at diagnosis. Besides rapidly decreasing eGFR, all presented with proteinuria around 1.5 g/day and dysmorphic microhematuria, suggesting glomerular inflammation. Systemic symptoms suggestive for ANCA vasculitis were seen in half of our patients, but only one patient had hemorrhagic alveolitis. Patients from our cohort responded to the intensive immunosuppressive regimens used in ANCA-positive vasculitis with renal involvement. However, in the follow-up, one patient had a relapse followed by septic shock related to immunosuppression and one patient started hemodialysis. In the review, we found that IgAN-ANCA -positive patients are characterized by vasculitis-like lesions and clinically by a rapidly progressive decline in kidney function, which was reversed by an aggressive induction immunosuppressive protocol used in ANCA vasculitis. Checking ANCA serology seems useful in patients with rapidly progressive IgAN for therapeutic and prognostic reasons.

Background World Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S. haematobium and S. mansoni morbidities in school-age children. Methodology A total of 22,488 children aged 6–15 years from monitoring and evaluation cohorts in Burkina Faso, Mali, Niger, Uganda, Tanzania, and Zambia from 2003–2008 were analyzed using Bayesian logistic regression. Models were utilized to evaluate associations between intensity categories and the prevalence of any urinary bladder lesion, any upper urinary tract lesion, microhematuria, and pain while urinating (for S. haematobium) and irregular hepatic ultrasound image pattern (C-F), enlarged portal vein, laboratory-confirmed diarrhea, and self-reported diarrhea (for S. mansoni) across participants with infection and morbidity data. Principal findings S. haematobium infection intensity categories possessed consistent morbidity prevalence across surveys for multiple morbidities and participants with light infections had elevated morbidity levels, compared to negative participants. Conversely, S. mansoni infection intensity categories lacked association with prevalence of the morbidity measures assessed. Conclusions/significance Current status infection intensity categories for S. haematobium were associated with morbidity levels in school-age children, suggesting urogenital schistosomiasis morbidity can be predicted by an individual’s intensity category. Conversely, S. mansoni infection intensity categories were not consistently indicative of childhood morbidity at baseline or during the first two years of a preventive chemotherapy control program., Author summary Infections with Schistosoma parasites are commonly classified by the presence and concentration of excreted Schistosoma eggs. Guidelines put forward by the World Health Organization (WHO) include classifications of S. haematobium infections assessed by urine filtration into light and heavy infections and S. mansoni infections assessed by Kato-Katz thick smears into light, moderate, and heavy infections. Past evidence has demonstrated an association between intensity of infection with morbidity for severe morbidities, but this was before recognition of the effect of light-intensity infections on morbidity and was done in treatment naïve populations. In these analyses, we assessed the associations between the WHO classifications for infection intensity and a wide array of S. haematobium and S. mansoni morbidity indicators in school-age children ascertained in monitoring and evaluation cohorts before and after initiation of deworming. Our analyses found a high correlation with S. haematobium intensity categories and morbidity indicators, especially microhematuria, but weaker correlation between S. mansoni intensity categories and morbidity indicators. The results indicate that, on the aggregate, the intensity categories represent a person’s S. haematobium-related morbidity but are poor at representing a person’s S. mansoni-related morbidity.

Objective To explore how laboratories in the United States (U.S.) report red blood cell per high powered field (RBC/HPF) counts on urinalysis and to evaluate whether this methodology permits effective risk stratification in accordance with the 2020 AUA/SUFU microhematuria guidelines. Materials and Methods Reporting methods for RBC/HPF counts (ranges, or actual counts) were collected by querying urologists in U.S. academic medical institutions or commercial laboratories. We explore whether (1) the reporting schemes were concordant with the risk strata in the new microhematuria guideline (3-10 [low risk], 11-25 [intermediate risk], and more than 25 [high risk]), and (2) evaluate the potential for risk group misclassification based on reporting methodology. Results Data were available for 141 laboratories. Seventy-two (51%) use RBC/HPF ranges, while the remainder use actual counts (or counts to a threshold). Sixty (42%) report range cutoffs which are not concordant with the microhematuria guidelines risk groups. Furthermore, fifty-six (40%) do not include the cutoff of 25 RBC/HPF which could potentially misclassify intermediate and high risk groups. Finally, sixteen (11%) do not include the cut-off of 3 RBC/HPF that defines the presence of microhematuria. Conclusion A significant number of laboratories report RBC/HPF counts in ranges that differ from thresholds in the 2020 AUA/SUFU guideline. The implication is potential misclassification of microhematuria both at minimum threshold diagnosis (3 RBC/HPF), and additionally between intermediate and high risk groups. Standardization of reporting schemes to actual RBC/HPF counts may allow improved adherence to guidelines while providing data for future guideline development.

Purpose The American Urological Association guideline for asymptomatic microhematuria recommends in patients with a negative initial workup, repeat workup should be considered for those with persistent/recurrent microhematuria. However, there is little data on the yield of repeat evaluation. Our hypothesis was that repeat workup yields a low detection rate of urologic malignancy. Materials and Methods We retrospectively reviewed all patients at our institution who underwent microhematuria workup with cystoscopy and upper tract imaging from May 2010 to June 2016. Microhematuria was defined as ≥3 RBCs/HPF on a properly collected specimen in the absence of a benign cause. Demographics, age, smoking history, history of radiation, and findings on repeat cystoscopy and imaging were collected. Our primary endpoint was a new diagnosis of urologic malignancy. Results Our initial cohort included 1,332 patients, of whom 21 were diagnosed with urothelial carcinoma and 7 with suspicious renal masses on initial workup. A total of 637 patients with negative initial workup had persistent/recurrent microhematuria. Repeat cystoscopy was performed in 161 (25%) patients at a median of 39 months, and repeat upper tract imaging was performed in 317 (50%) patients at a median of 39 months. Overall, repeat cystoscopy revealed new bladder cancer in 2 (1.2%) patients and repeat imaging revealed new suspicious renal mass in 4 (1.3%) patients. Conclusions We observed a low number of newly diagnosed malignancies among patients with persistent/recurrent asymptomatic microhematuria who had a prior negative workup. Additional research is required to determine the utility of a repeat AMH workup.

Background: Genetically determined prelingual hearing loss (HL) may occur in an isolated or syndromic form. Objective: The aim of the study was to unravel the genetic cause of medical problems in a 21-year-old woman, whose phenotypic presentation extended beyond Stickler syndrome and included enlarged vestibular aqueduct (EVA) and persistent microhematuria. Methods and Results: After sequencing of clinical exome, a known de novo COL2A1 pathogenic variant (c.1833+1G>A, p.?) causative for Stickler syndrome and one paternally inherited pathogenic change in COL4A5 (c.1871G>A, p.Gly624Asp) causative for X-linked Alport syndrome were found. No pathogenic variants, including those within the SLC26A4 5′ region (Caucasian EVA haplotype), explaining the development of EVA, were identified. Conclusions: The study reveals a multilocus genomic variation in one individual and provides a molecular diagnosis of two HL syndromes that co-occur in the proband independent of each other. For the third entity, EVA, no etiological factor was identified. Our data emphasize the relevance of detailed clinical phenotyping for accurate genotype interpretation. Focus on broadening the phenotypic spectrum of known genetic syndromes may actually obscure patients with multiple molecular diagnoses.

Introduction: Emerging data have described poor clinical outcomes from infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) among African American patients and those from underserved socioeconomic groups. We sought to describe the clinical characteristics and outcomes of acute kidney injury (AKI) in this special population. Methods: This is a retrospective study conducted in an underserved area with a predominance of African American patients with coronavirus disease 2019 (COVID-19). Descriptive statistics were used to characterize the sample population. The onset of AKI and relation to clinical outcomes were determined. Multivariate logistic regression was used to determine factors associated with AKI. Results: Nearly half (49.3%) of the patients with COVID-19 had AKI. Patients with AKI had a significantly lower baseline estimated glomerular filtration rate (eGFR) and higher FiO2 requirement and D-dimer levels on admission. More subnephrotic proteinuria and microhematuria was seen in these patients, and the majority had a pre-renal urine electrolyte profile. Patients with hospital-acquired AKI (HA-AKI) as opposed to those with community-acquired AKI (CA-AKI) had higher rates of in-hospital death (52 vs. 23%, p = 0.005), need for vasopressors (42 vs. 25%, p = 0.024), and need for intubation (55 vs. 25%, p = 0.006). A history of heart failure was significantly associated with AKI after adjusting for baseline eGFR (OR 3.382, 95% CI 1.121–13.231, p = 0.032). Conclusion: We report a high burden of AKI among underserved COVID-19 patients with multiple comorbidities. Those who had HA-AKI had worse clinical outcomes compared to those who with CA-AKI. A history of heart failure is an independent predictor of AKI in patients with COVID-19.

C3 glomerulopathy (C3G) is a clinical spectrum that presents with a variety of symptoms, ranging from a mild disease with asymptomatic microhematuria and/or proteinuria to severe disease with nephritic or nephrotic syndrome and renal impairment. Herein, we aim to document the clinical and laboratory findings, response to immunosuppressive and supportive treatment and prognosis of the children with C3G. We retrospectively reviewed the medical records of patients diagnosed with membranoproliferative glomerulonephritis (MPGN). Kidney biopsy materials were reexamined for the diagnosis of C3G. The inclusion criteria for C3G are the dominant C3 staining with or without scanty immunoglobulins (Ig) deposition on immuno- fluorescence (IF) and MPGN patterns on light microscope. Twelve of 69 patients with MPGN were included in the study based on the definition criteria of C3G. Ten of them had only C3 staining and the rest of the patients had both C3 staining and a small amount of IgG/M staining on IF microscopy. One patient was on remission with only ACEI. The rest of the patients used immunosuppressive treatment and two of them needed eculizumab therapy. One of them did not respond to the treatment of eculizumab and progressed to end-stage renal failure. C3G is a disease characterized by a heterogeneous clinical presentation and outcome. Because of this broad spectrum of disease, treatment may vary widely. We think that complement-targeting therapy with eculizumab should be an alternative option for refractory cases, especially in the early stage of disease, if they did not respond to immunosuppressive treatment.

Hematuria is a common reason for patients to be referred for imaging of the urinary tract. All patients diagnosed with hematuria should undergo a thorough history and physical examination, urinalysis, and serologic testing prior to any initial imaging. Ultrasound, CT, and MRI are the most common imaging modalities used to evaluate hematuria. This document discusses the following clinical scenarios for hematuria: initial imaging of microhematuria without risk factors or history of recent vigorous exercise, or presence of infection, or viral illness, or present or recent menstruation; initial imaging of microhematuria in patients with known risk factors and no history of recent vigorous exercise, or presence of infection, or viral illness, or present or recent menstruation or renal parenchymal disease; initial imaging of microhematuria in the pregnant patient and initial imaging of gross hematuria. Follow-up of normal or abnormal findings is beyond the scope of this review. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

In April 2012, a group of nephrologists organized a consensus conference in Cambridge (UK) on type II membranoproliferative glomerulonephritis and decided to use a new terminology, “C3 glomerulopathy” (C3 GP). Further knowledge on the complement system and on kidney biopsy contributed toward distinguishing this disease into three subgroups: dense deposit disease (DDD), C3 glomerulonephritis (C3 GN), and the CFHR5 nephropathy. The persistent presence of microhematuria with or without light or heavy proteinuria after an infection episode suggests the potential onset of C3 GP. These nephritides are characterized by abnormal activation of the complement alternative pathway, abnormal deposition of C3 in the glomeruli, and progression of renal damage to end-stage kidney disease. The diagnosis is based on studying the complement system, relative genetics, and kidney biopsies. The treatment gap derives from the absence of a robust understanding of their natural outcome. Therefore, a specific treatment for the different types of C3 GP has not been established. Recommendations have been obtained from case series and observational studies because no randomized clinical trials have been conducted. Current treatment is based on corticosteroids and antiproliferative drugs (cyclophosphamide, mycophenolate mofetil), monoclonal antibodies (rituximab) or complement inhibitors (eculizumab). In some cases, it is suggested to include sessions of plasma exchange.

IgA nephropathy (IgAN), or Berger's disease, is the most common primary glomerular disease worldwide, but varies largely in its geographic distribution. A systematic review of 1,619 publications from the five continental regions of the world was performed to assess the prevalence of IgAN in different worldwide regions and analyze factors responsible for geographic differences. All observational studies that described the prevalence and incidence data on glomerulonephritis were considered. IgAN is more frequent in Asian populations (45 cases per million population/y in Japan) than in Caucasians (31 cases per million population/y in France). These differences are owing to some relevant aspects: (1) systematic mass screening of urine in populations, as occurring in some Asian countries (Hong Kong, Japan, Korea, and Singapore), is not common in Western countries; (2) general practitioners and health care professionals in Western countries underestimate persistent microscopic hematuria and/or mild proteinuria in apparently healthy individuals causing late referral to a nephrologist; and (3) nephrologists adopt different indications for kidney biopsy in individuals with persistent urinary abnormalities. In addition, differences also are owing to the source of data, because the frequency of IgAN observed in a nephrology center with a high incidence of kidney biopsies is higher than in a regional renal biopsy registry that receives data from many centers. In conclusion, greater efforts should be made to diagnose IgAN earlier in individuals who manifest persistent microhematuria and/or mild proteinuria and to introduce less stringent indications for kidney biopsies. This preventive approach, followed by early therapy, may reduce the global burden of end-stage kidney disease caused by IgAN.

Background Microhematuria is common in immunoglobulin A nephropathy (IgAN). However, current prognostication is based on proteinuria and mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, tubulointerstitial fibrosis and crescent (MEST-C) scores. Methods In this retrospective study, we evaluated whether MEST-C score components are associated with the presence of microhematuria at biopsy and whether the degree of microhematuria during follow-up is associated with change in estimated glomerular filtration rate (eGFR), after adjusting for clinical and histological parameters. We identified 125 patients with biopsy-proven IgAN and MEST-C scoring who were not on immunosuppressive therapy at biopsy. Microhematuria was defined as ≥3 red blood cells (RBCs)/high-power field (hpf). Results Of the 125 patients, 97 had microhematuria at baseline and were more likely to have M1, E1 and C ≥ 1 lesions (P Conclusion Degree of microhematuria during follow-up is an independent predictor of eGFR decline after adjusting for clinical and histological parameters. Therefore, monitoring the degree of microhematuria as well as proteinuria is important when evaluating patients with IgAN. Additional studies using improvement in microhematuria as a primary surrogate outcome are needed.

Urine erythrocyte (Ery) and leukocyte (Leu) dipstick tests are essential for detecting microhematuria and urinary tract infection. Currently, there is no suggestion for establishing the cut-off limits in an ordinal scale test. This study aimed to establish the cut-off limits for urine Ery and Leu dipstick tests via probit regression. From 1 January 2016 to 30 June 2016, laboratory data were collected from patients at one teaching hospital whose specimen had analytical results from both a urine dipstick test and an automated urine particle analyzer. Probit regression was used to estimate the probability of positive urine dipstick results as a function of log-transformed urine Ery and Leu concentrations. Based on the analysis of 22,122 specimens, the estimated concentration that yields 50% positive results (C50) of the Ery weak+, 1+, 2+, 3+, and 4 + dipstick results were 14.6, 40.4, 51.6, 136.3 and 219.0 × 106/L, respectively. The estimated C50 of the Leu 1+, 2+ and 3 + dipstick results were 22.7, 67.9 and 283.9 × 106/L, respectively. The estimated values were different from arbitrary concentrations provided for each dipstick category by the manufacturer. If a quantitative comparison method/procedure is available, the cut-off limits of an ordinal scale test can be established using probit regression. Each laboratory should investigate the transferability of the arbitrary concentrations provided by the manufacturer, and if necessary, determine its own cut-off limits of urine Ery and Leu dipstick tests.

Rationale & Objective: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS). Study Design: Retrospective cohort study. Setting & Participants: 82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected. Observations: A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P = 0.8), causative genes (P = 0.6), or type of variant (P = 0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was -1.46 (-1.66 to -1.26) mL/min/1.73 m(2) per year for the overall group, with no significant differences between ADAS genes (P = 0.2). Limitations: The relatively small size of this series from a single country, potentially limiting generalizability. Conclusions: Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using next generation sequencing (NGS) for 5 genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, 9 of them novel. In 5 families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, 8 (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-years, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies.

A 30-year-old man, who had moved to the United Kingdom from South Asia, was referred to the renal clinic with nephrotic syndrome. He had recently been diagnosed with systemic lupus erythematosus (SLE) after presenting to the rheumatology clinic with joint pain, skin rash, and pleuritic chest pain and fulfilling 8 of 17 SLICC (Systemic Lupus International Collaborating Clinics) diagnostic criteria.1 His immunology was in keeping with active SLE: his complement levels were low, and he had antibodies against double-stranded DNA and extractable nuclear antigens (Table S1A in the online-only Data Supplement). Our patient had heavy proteinuria (3.9 g/d) and a low serum albumin (25 g/L) in keeping with the nephrotic syndrome. Although his excretory renal function was normal, he had microhematuria (3+) on urinalysis. An urgent renal tract ultrasound with Doppler revealed that he had a preexistent renal vein thrombosis for which he was anticoagulated. In the absence of any serological evidence of antiphospholipid syndrome, this was attributed to his nephrotic syndrome. He went on to have a renal biopsy. This demonstrated classes III (focal proliferative) and V (membranous) lupus nephritis (Figure 1). Figure 1. Initial glomerular histology. A , Normal glomerulus. Single arrow: Normal capillary wall. This should be a similar thickness to the tubular epithelium (arrowhead). Double arrow: Normal mesangium. B , Classes III (focal proliferative) and V (membranous) lupus nephritis. Single arrow: Thickened capillary wall. Double arrow: Focal proliferation. At presentation, his blood pressure (BP) was 126/88 mm Hg in the absence of antihypertensive treatment. Although this lay within both UK and US recommended guidelines, …

Introduction This study aimed to demonstrate the clinical utility of non-invasive multigene Cxbladder urine tests in reducing the overall number of diagnostic tests and invasive procedures used in the clinical evaluation of patients presenting with microhematuria, a key symptom of urothelial carcinoma (UC). There is a belief that using non-invasive molecular diagnostic tests in patients with hematuria may lead to patients undergoing unnecessary and costly invasive procedures that can cause adverse events and decrease patient quality of life. The objective of this study was to determine whether or not this was the case, using Cxbladder. Methods Data from 396 patient-by-urologist interactions generated 792 decision points from a standardized cohort of 33 patients evaluated by 12 urologists. Participant physicians recommended a selection of tests and procedures based on referral data, then reviewed and amended their recommendations in the context of diagnostic information from Cxbladder used in the Triage and Triage and Detect clinical modalities. Results All urologists changed their diagnostic behavior in at least one patient case with the addition of Cxbladder results. The total number of diagnostic procedures was reduced by 5% and 25% following disclosure of results from Cxbladder in the Triage and the Triage and Detect modalities, respectively. The total number of requested invasive procedures was reduced from 425 at referral to 379 (−11%) and 292 (−31%) following disclosure of Cxbladder information in the Triage and Triage and Detect modalities, respectively. Conclusions Urologists made compelling changes to their clinical decision-making when they were provided with Cxbladder results for patients presenting with hematuria. Cxbladder provides an increase in clinical utility by focusing the use of invasive diagnostic procedures to appropriate patients, reducing both the total number and number of invasive procedures used in the clinical management of patients with hematuria, thereby improving the diagnostic experience and outcomes for patients. Funding Pacific Edge Ltd. Electronic supplementary material The online version of this article (doi:10.1007/s12325-017-0518-7) contains supplementary material, which is available to authorized users.

OBJECTIVES The objectives of this were to determine the correlation of greater than or equal to 3 red blood cells per high-power field (RBCs/HPF) with a positive urine dipstick for blood and to identify clinically relevant factors than can influence this relationship. METHODS The charts of women with positive blood urine dipsticks were reviewed from August 2012 to August 2013. The cohort of women was divided into 2 groups; those with urine with greater than or equal to 3 RBCs/HPF on microscopy and those without. Relevant clinical and demographic variables were extracted from the electronic medical record. Data analysis was conducted using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS Most of the 203 patients eligible for analysis were Caucasian, and the total cohort had a mean age of approximately 62.8 years. Microscopy confirmed greater than or equal to 3 RBCs/HPF in 25.6% of the urine samples. A dipstick finding of moderate or large blood was significantly more likely to have greater than or equal to 3 RBCs/HPF on univariate and multivariable analyses (P < 0.001). Factors significantly associated with greater than or equal to 3 RBCs/HPF were increasing age, recurrent urinary tract infections, and urinary specific gravity of greater than 1.010. CONCLUSIONS Lower urinary specific gravities appear to be associated with underestimating microhematuria, likely owing to the underrepresentation of the true number of red blood cells. Urine dipstick indicators of moderate or large blood increase the likelihood the microscopy samples demonstrated greater than or equal to 3 RBCs/HPF. These findings suggest that clarification of microhematuria detection and evaluation guidelines should be considered, given both important clinical and economic consequences.

Background This systematic review and meta-analysis aims to investigate the prevalence of microhematuria in patients presenting with suspected acute renal colic and/or confirmed urolithiasis at the emergency department. Methods A comprehensive literature search was conducted to find relevant data on prevalence of microhematuria in patients with suspected acute renal colic and/or confirmed urolithiasis. Data from each study regarding study design, patient characteristics and prevalence of microhematuria were retrieved. A random effect-model was used for the pooled analyses. Results Forty-nine articles including 15′860 patients were selected through the literature search. The pooled microhematuria prevalence was 77% (95%CI: 73–80%) and 84% (95%CI: 80–87%) for suspected acute renal colic and confirmed urolithiasis, respectively. This proportion was much higher when the dipstick was used as diagnostic test (80 and 90% for acute renal colic and urolithiasis, respectively) compared to the microscopic urinalysis (74 and 78% for acute renal colic and urolithiasis, respectively). Conclusions This meta-analysis revealed a high prevalence of microhematuria in patients with acute renal colic (77%), including those with confirmed urolithiasis (84%). Intending this prevalence as sensitivity, we reached moderate values, which make microhematuria alone a poor diagnostic test for acute renal colic or urolithiasis. Microhematuria could possibly still important to assess the risk in patients with renal colic.

A 68-year-old male with gastric cancer was treated with tegafur/gimeracil/oteracil and oxaliplatin for 6 months. Thereafter, he was treated with paclitaxel and ramucirumab for 3 months. However, neither regimen had much effect. Thus, he was treated with nivolumab for 2 months, but he developed proteinuria, microhematuria, and an acute kidney injury. A kidney biopsy revealed occasional swollen endothelial cells and proliferating mesangial cells. Few abnormal findings were seen in the tubules or interstitial tissue. Immunofluorescent staining showed segmental immunoglobulin A and complement component 3 deposition, in the mesangial area. Electron microscopy showed a small amount of electron-dense deposits in the paramesangial area and swollen endothelial cells. Mesangial interposition, the loss of endothelial cell fenestration, and subendothelial edema were also observed. Furthermore, foot process effacement and villous transformation of epithelial cells were noted. After the discontinuation of nivolumab, the patient’s renal function gradually improved, and his proteinuria disappeared. Nivolumab treatment was restarted at that time because of cancer progression; however, it was ineffective. No occult blood was detected from 7 months after the administration of the last dose of nivolumab. This is a unique case, in which a kidney biopsy revealed evidence of nivolumab-associated glomerular endothelial injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13730-021-00610-0.

OBJECTIVE: To describe the clinical and ultrasound characteristics of urinary bladder malignancies diagnosed on transvaginal ultrasound in women presenting with suspected gynecological problems. METHODS: This was a multicenter retrospective study of women with a histological diagnosis of urinary bladder malignancy that was suspected on transvaginal ultrasound examination. The cases were collected from three centers that specialize in the use of pelvic ultrasound and had been examined between January 2007 and October 2018. Clinical data were obtained from the computer databases and all tumor images were assessed by two of the authors (D.J. and J.K.) to identify characteristic sonographic patterns. We compared the characteristics of tumors between women presenting with symptoms suspicious of urinary bladder malignancy and those without such symptoms. RESULTS: Thirty women with a confirmed diagnosis of urinary bladder malignancy on histological examination were included. Median age at diagnosis was 70.5 (range 36-88) years. The most common presenting symptom was postmenopausal bleeding, which was recorded in 18 (60%) women. Ten (33%) women had symptoms suspicious of bladder malignancy, of whom six had unexplained visible hematuria, three had unexplained recurrent urinary tract infections and one had dysuria and microhematuria. On histological examination, 23 (77%) women were diagnosed with primary bladder malignancy whilst seven (23%) had metastases in the bladder from other primary tumors. Out of 23 primary tumors, 21 (91%) were of urothelial origin (12 low grade and nine high grade). Most low-grade urothelial carcinomas appeared on ultrasound as irregular papillary growth (11/12, 92%) and were moderately to highly vascular on color Doppler examination (8/12, 67%). The ultrasound appearances of primary non-urothelial and metastatic tumors varied, without a clear common morphological tumor pattern. The tumors found in women with symptoms suggestive of bladder malignancy did not differ unequivocally from those detected in other women in terms of size, ultrasound morphology, vascularity or histological type. CONCLUSION: Urinary bladder malignancies can be detected in patients undergoing transvaginal ultrasound examination for suspected gynecological problems. Primary urothelial cancers have a relatively uniform morphological pattern, whilst the appearances of other bladder malignancies are more variable. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:56 issue:3 pages:453-459 ispartof: location:England status: published

Background Alport syndrome is a rare genetic kidney disease, and rheumatoid arthritis as a common autoimmune disease also causes renal lesions in addition to arthritis. The overlap of them has rarely been reported. Case presentation A 44-year-old man had a history of multi-joint swelling and pain for more than half a year. His laboratory data with double positive for rheumatoid factor and anticitrullinated protein antibodies further supported the diagnosis of early rheumatoid arthritis. His previous medical history including progressive hearing loss for several years and microhematuria for one year attracted our attention. Renal biopsy showed thin basement membrane nephropathy and lymphocytes infiltration of interstitium. To make a precise diagnosis, targeted Next Generation Sequencing (NGS) of an inherited renal disease panel including Alport syndrome genes was performed, which revealed the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Further in silico analyses predicted that the p. Cys451Arg mutation is functionally “damaging”, so the diagnosis of Alport syndrome was finally proved. The patient has been receiving the treatment of total glucosides of paeony and leflunomide for rheumatoid arthritis, and Cozaar 50 mg for the protection of kidney so far. During the 10-months follow-up, swelling and tenderness of the joints in this patient had been generally relieved, with no obvious improvement in microhematuria and a slight increase in proteinuria. Conclusion we reported an adult man with the coexistence of rheumatoid arthritis and Alport syndrome with the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Whether the overlap of them is occasional or has a common pathophysiological mechanism is still unclear.

Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of hematuria and progression of IgAN.Retrospective cohort study.A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months.Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/μL (automated method) during the first 6 months of follow-up.Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure.Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event.Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P 0.001), and results using these 2 methods were consistent.A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated.Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.

ANCA-associated vasculitis (AAV) are the prototype of a disease characterised by the presence of a biomarker; ANCA positivity in fact is recorded in 90% of cases of GPA and MPA. The role of ANCA in the management of AAV ranges from diagnostic to prognostic purposes with also therapeutic implications. Changes in clinical practice with the increased use of rituximab have drawn attention to B-cells as a biomarker able to contribute to patient management. Cytokines and other circulating factors, although still at a research stage, may represent future biomarkers of interest or even therapeutic options. From the point of view of renal involvement in AAV, proteinuria and microhematuria are still the biomarkers employed in everyday clinical practice with a proposed role for emerging ones (MCP1, CD163 and CD25). The aim of this review is to discuss the role of well-known biomarkers in everyday clinical management of AAV patients as well as future perspectives for those that are still at a research stage with attention to therapeutic implications.

A 31-year-old woman presented at the emergency room after experiencing colic pain in the right iliac fossa for 5 days. She had previously consulted another center, where deterioration of renal function had been identified and abdominal computed tomography (CT) angiography had shown a dissection of the right renal artery, with areas suggestive of infarction in the right kidney, as well as an aneurysm in the left renal artery and a smaller left kidney. The patient had no relevant family or personal history except posttraumatic carotid-cavernous fistula in 2014, which had been treated with embolization. In our hospital, the patient was hypertensive and acute renal failure was confirmed, accompanied by an increase in lactate dehydrogenase and isomorphic microhematuria. After a new CT Scan, in addition to the lesions described in the renal arteries, another aneurysm in the splenic artery and an aneurysm of the right femoral artery were identified. Antihypertensive treatment was initiated with calcium antagonists and anticoagulation. Subsequent renal arteriography confirmed the dissection of the right renal artery, which could not be repaired, and a coated stent was placed in the left renal artery to exclude the aneurysm. The splenic artery lesion was treated 2 months later. The etiological diagnosis in this young woman was challenging. The presence of visceral aneurysms suggested a differential diagnosis comprising fibromuscular dysplasia, vasculitis, and collagenopathies. Using a multidisciplinary approach and directed anamnesis, the presence of frequent sprains, joint hypermobility, and skin fragility was confirmed. Blood immunology and CT angiography including the thoracic and cervical territories were normal. Echocardiography revealed tricuspid insufficiency. All these data suggested the presence of a collagen-like Ehlers-Danlos syndrome (vascular form). The diagnosis was confirmed by the genetic study, which showed a pathogenic mutation in the COL3A1 gene. Currently, the patient is asymptomatic with recovered renal function following treatment with a beta-blocker and antiplatelet therapy.